PROJECT SUMMARY/ABSTRACT Chronic pain is one of the most prevalent conditions in the U.S. affecting more than 100 million adults, particularly older adults aged 65 years and above. It is also an important public health problem with significant medical, social, and economic consequences. Opioids are currently used over long periods by millions of aging Americans to manage chronic cancer-related and non-cancer-related pain; however, limited knowledge is available on the prevalence, effectiveness, and safety of long-term use of opioids for physicians and patients to select the right dose and formulation of opioid therapy. We propose to (1) investigate the prevalence of long-term opioid use in older adults by underlying disease types, among high risk subpopulations, and across geographic locations; (2) evaluate the relationship between opioid dose, opioid formulation and risk of opioid- related adverse drug events in patients receiving long-term opioid therapy for chronic non-cancer pain (CNCP), therefore providing evidence regarding the safety and tolerability of opioid medications among older people; and (3) evaluate whether the relationship between opioid dose, opioid formulation and opioid-related adverse drug events are moderated by certain age-related factors using the 2013-2015 5% national sample of Medicare administrative claims data. Specifically, we hypothesize that among older adults using long- term opioid therapy: (1) higher doses are associated with increased opioid-related adverse drug events; (2) extended-release/long-acting (ER/LA) opioids are more likely to be associated with opioid- related adverse drug events compared to immediate release (IR) opioids; and (3) certain age-related factors are mediators of the relationship between long-term opioid dose/formulation and the risks of opioid-related adverse drug events. Through two Specific Aims, this proposed research will investigate the prevalence and safety of long-term opioid use among older adults. In Specific Aim 1, we will conduct a retrospective cohort study to estimate the prevalence of long-term opioid use among older adults in general, by underlying diseases, among high risk sub-populations, and by state of residence. In Specific Aim 2, we will conduct a retrospective cohort study to demonstrate that among older adults using long-term opioid therapy higher opioid doses and ER/LA formulations are more likely to be associated with opioid-related adverse drug events compared to lower doses and IR opioid formulation, respectively; and certain age-related factors are moderators of the relationship between long-term opioid dose/formulation and the risks of opioid-related adverse drug events. America is facing a nationwide crisis of prescription opioid diversion, misuse and abuse, and fatal overdoses involving prescription opioids, results from our research will provide the much needed scientific evidence on the epidemiology of opioid use in older adults as well as the benefits and risks of long- term opioid therapy in older adults in general and in subpopulations who might be at higher risk for adverse outcomes.